Patients with epidermal growth factor receptor (EGFR) exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but have a poorer response, according to a recent study.
Exon 20 mutations are the third most common family of EGFR mutations found in non-small cell lung cancer (NSCLC). Currently, little is known about cancers harboring these mutations, aside from their lack of response to EGFR tyrosine kinase inhibitors. This has impaired the development of effective targeted therapies.
A total of 1,086 patients who underwent EGFR genotyping between 2004 and 2012 were studied. To examine the exon 20 insertions, the research team identified cancers with exon 20 insertions, characterized their sequences, and retrospectively reviewed the effectiveness of different treatment regimens.
No significant differences were identified between the cancers carrying exon 20 insertions and those with the common EGFR mutations. However, cancers with exon 20 insertions were more commonly seen in patients who were never-smokers and in Asian patients. The median survival of patients with exon 20 insertions was 16 months, which is similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations.
These findings led the researchers from the Dana-Farber Cancer Institute to “estimate that lung cancers with EGFR exon 20 have an annual incidence of approximately 2,000 to 4,000 people in the United States, not dissimilar from the expected incidence of other uncommon genotype-defined subsets of NSCLC such as those with ROS1 rearrangements, BRAF mutations, or HER2 insertions.”
The researchers concluded, “previously treated NSCLC carrying EGFR exon 20 insertions represent a population on oncogene-addicted cancers in need of targeted therapy development.”
This study was published in the Journal of Thoracic Oncology (2013; doi:10.1097/JTO.0b013e3182779d18).